Skin grafts are often necessary for the treatment of severe, full-thickness burns, non-healing skin ulcers and other surgical operations where there is loss of skin or a need for skin coverage of soft tissue. The graft procedure involves placing a layer of healthy skin on the wound site. The graft serves to close the wound, protecting the underlying tissue to facilitate healing. Two main classifications of skin graft surgery, autograft and allograft, depend on the source of the donor tissue. In an autograft operation, the skin graft is harvested from a different location on the patient. In an allograft operation, the graft is harvested from an external source such as another donor (e.g., cadaver) or is prepared artificially (e.g., dermal equivalent).
Previous work done in the field of tissue engineering has produced skin grafts that may be used in surgery. Generally, the tissue graft may be produced by seeding a collagen matrix or other biocompatible material with the appropriate cells to create the desired culture. As the cells proliferate, the matrix degrades and is eventually replaced by a layer of healthy tissue. This layer of tissue or the matrix seeded with cells may be used in skin graft surgery.
Recent advances in tissue engineering based wound dressings have resulted in the emergence of a range of dermal, epidermal and even complete skin equivalents. Advances in cellular biology and knowledge in wound healing and growth factors have provided a wide variety of choices to attack the problem of the complex wound. Continued research and new developments have improved the level of care in the field of complex burn wound care and has resulted in the availability of epidermal, dermal and total skin substitutes.
For example, Epicel, a cultured epidermal autograft (CEA), is one of the early tissue engineered products. It is an epidermis cultured in vitro and not a true skin equivalent which may limit its range of potential uses. CEA requires several weeks to produce, has a low rate of graft take, is very fragile, is susceptible to infection, and is not suitable for use without a dermal layer. To address the above problems, composites consisting of dermal equivalents in combination with epidermal components were developed. A typical engineered skin substitute (ESS) is composed of an epidermal substitute of autologous keratinocytes, attached to a dermal analogue of collagen or collagen-glycosaminoglycan combination populated with autologous fibroblasts. Following in vitro culture prior to grafting, ESS demonstrates morphogenesis similar to native human skin.
However, current efforts to produce suitable dermal equivalents are complicated by the multiple layers and corresponding functions that must be present. For example, the external layer must be capable of closing the wound and providing protection to the underlying tissue. Internal layers must be conducive to the formation of blood vessels and circulation. The state-of-the-art techniques in tissue engineered skin rely on the sequential culture of dermal fibroblasts and keratinocytes on a collagen matrix. The culture process relies on a relatively long culture time to increase cell numbers within the construct before a suitable dermal equivalent has been produced.